Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Department of Diagnostic and Public Health, Section of Pharmacology, University of Verona, Verona, Italy.
Br J Pharmacol. 2017 Oct;174(19):3333-3345. doi: 10.1111/bph.13952. Epub 2017 Aug 19.
Methoxetamine (MXE) is a novel psychoactive substance that is emerging on the Internet and induces dissociative effects and acute toxicity. Its pharmacological effects have not yet been adequately investigated.
We examined a range of behavioural effects induced by acute administration of MXE (0.5-5 mg·kg ; i.p.) in rats and whether it causes rapid neuroadaptive molecular changes.
MXE (0.5-5 mg·kg ) affected motor activity in a dose- and time-dependent manner, inducing hypermotility and hypomotility at low and high doses respectively. At low and intermediate doses (0.5 and 1 mg·kg ), MXE induced anxious and/or obsessive-compulsive traits (marble burying test), did not significantly increase sociability (social interaction test) or induce spatial anxiety (elevated plus maze test). At a high dose (5 mg·kg ), MXE induced transient analgesia (tail-flick and hot-plate test), decreased social interaction time (social interaction test) and reduced immobility time while increasing swimming activity (forced swim test), suggesting an antidepressant effect. Acute MXE administration did not affect self-grooming behaviour at any dose tested. Immunohistochemical analysis showed that behaviourally active doses of MXE (1 and 5 mg·kg ) increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex and hippocampus.
MXE differentially affected motor activity, behaviour and emotional states in rats, depending on the dose tested. As reported for ketamine, phosphorylation of the ribosomal protein S6 was increased in MXE-treated animals, thus providing a 'molecular snapshot' of rapid neuroadaptive molecular changes induced by behaviourally active doses of MXE.
甲氧基卡西酮（MXE）是一种新型精神活性物质，正在互联网上兴起，具有致分离效果和急性毒性。其药理作用尚未得到充分研究。
我们研究了 MXE（0.5-5mg·kg；ip）急性给药在大鼠中引起的一系列行为效应，以及是否引起快速神经适应的分子变化。
MXE（0.5-5mg·kg）以剂量和时间依赖的方式影响运动活动，分别在低剂量和高剂量下引起过度运动和运动减少。在低剂量和中等剂量（0.5 和 1mg·kg）下，MXE 诱导焦虑和/或强迫行为（埋珠试验），不显著增加社交性（社交互动试验）或诱导空间焦虑（高架十字迷宫试验）。在高剂量（5mg·kg）下，MXE 诱导短暂的镇痛（尾巴摆动和热板试验），减少社交互动时间（社交互动试验），同时增加游泳活动（强迫游泳试验），减少不动时间，提示抗抑郁作用。急性 MXE 给药在任何测试剂量下均不影响自我修饰行为。免疫组织化学分析表明，行为活性剂量的 MXE（1 和 5mg·kg）增加了内侧前额叶皮层和海马中的核糖体蛋白 S6 的磷酸化。
MXE 根据测试剂量，不同程度地影响大鼠的运动活动、行为和情绪状态。与氯胺酮一样，核糖体蛋白 S6 的磷酸化在 MXE 处理的动物中增加，从而提供了行为活性剂量的 MXE 诱导的快速神经适应分子变化的“分子快照”。
